Enormous effort is now being focused on the development and implementation of molecular genetic technologies to identify genes and mutations associated with predisposition to common diseases and health risks. These efforts will provide key novel insights into disease etiology, and generate DNA-based diagnostic/prognostic tools for improved clinical therapies. In this phase I Small Business Innovation Research (SBIR) application, we propose to adapt flow cytometric microsphere technology available from Luminex Corporation, to validate a powerful, rapid, cost-effective strategy that would permit the genotyping of multiple variants of genes simultaneously, initiating our analysis with screening for CYP2D6 single nucleotide polymorphisms (SNPs). Luminex technology combines advances in computing and optics with a new concept in color-coding to create a simple, efficient analysis system with considerable potential for SNP detection. We propose to design, validate and optimize probes for twelve of the most common CYP2D6 SNPs accounting for the majority of poor metabolizers (approximately 93 percent of all CYP2D6 alleles) and will formulate a library of microspheres for subsequent multiplexing. We will also optimize the multiplex assay approach, using the most common SNPs on exons 2,6,8 as the initial model. In Phase II, we will validate this technology by relating genotype results to in vivo CYP2D6 activity and will extend the range of SNPs screened to cover all nine exons in a multiplexed format. Commercial Application: This project will demonstrate a high throughput, cost effective alternative for genotyping analyses. Screening for CYP2D6 SNPs is an important molecular diagnostic tool for the enhancement of patient care and drug therapy and for pharmacogenomic based research in clinical trials and molecular epidemiological studies. Additional metabolic enzyme genetic endpoints will be added for SNP screening in the future.